A Case of Concurrent Hypogammaglobulinemia, Cancer, and Cardiomyopathy: A Beta-Catenin Connection?
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Camellia Hernandez, MD, Cecilia Mikita, MD MPH FAAAAI

Hypogammaglobulinemia is a humoral immune deficiency characterized by impaired antibody production resulting in recurrent infections.  We present a case of hypogammaglobulinemia in an individual with primary lung adenocarcinoma and nonischemic cardiomyopathy caused by a desmoplakin gene mutation.


Clinical exams, imaging, biopsy, and laboratory evaluation


 A 55 year old male active duty service member presents with chronic infectious rhinosinusitis. Symptoms arose on deployment to Iraq, where he exhibited persistent URI symptoms.  Upon returning to the US, he developed multiple sinopulmonary infections requiring antibiotic treatment at 1-2 months intervals. Diagnostic testing revealed lymphopenia and decreased levels of IgG and IgM.  Pneumovax administration resulted in an adequate immune response, though his clinical picture was most consistent with hypogammaglobulinemia NOS.  He remained asymptomatic, until, he experienced a syncopal event while running. TTE revealed a reduced ejection fraction of 25%.  A cardiomyopathy panel revealed a mutation of the desmoplakin (DSP) gene. A CT scan of the chest noted a 6mm opacity of the right upper lobe and a lobectomy with resultant pathology was consistent with two invasive adenocarcinomas.


Defects of the DSP protein are associated with dilated cardiomyopathy and lung carcinoma through inhibition of desmoplakin tumor suppressor function via the wnt/beta-catenin signaling pathway.  Beta-catenin also facilitates transcription of proteins essential to B cell development.  This case provides an opportunity to review the role of the beta-catenin signaling pathway and the contribution of desmoplakin gene transcription in B cell differentiation. Investigation of pathway dysfunction may provide opportunities for targeted therapy in hypogammaglobulinemia.